title: Impact of C-peptide preservation on metabolic and clinical outcomes in the Diabetes Control and Complications Trial.
abstract: The Diabetes Control and Complications Trial established that a stimulated C-peptide concentration ≥0.2 nmol/L at study entry among subjects with up to a 5-year diabetes duration is associated with favorable metabolic and clinical outcomes over the subsequent 7 years of follow-up. Herein we further examine the association of both fasting and stimulated C-peptide numerical values with outcomes. In the intensive treatment group, for a 50% higher stimulated C-peptide on entry, such as from 0.10 to 0.15 nmol/L, HbA1c decreased by 0.07% (0.8 mmol/mol; P = 0.0003), insulin dose decreased by 0.0276 units/kg/day (P < 0.0001), hypoglycemia risk decreased by 8.2% (P < 0.0001), and the risk of sustained retinopathy was reduced by 25% (P = 0.0010), all in unadjusted analyses. Other than HbA1c, these effects remained significant after adjusting for the HbA1c on entry. While C-peptide was not significantly associated with the incidence of nephropathy, it was strongly associated with the albumin excretion rate. The fasting C-peptide had weaker associations with outcomes. As C-peptide decreased to nonmeasurable concentrations, the outcomes changed in a nearly linear manner, with no threshold or breakpoint. While preservation of stimulated C-peptide at ≥0.2 nmol/L has clinically beneficial outcomes, so also does an increase in the concentration of C-peptide across the range of values.
authors.affiliation: The Biostatistics Center, The George Washington University, Rockville, MD.
authors.forename: John M
authors.initials: JM
authors.lastname: Lachin
authors.forename: Paula
authors.initials: P
authors.lastname: McGee
authors.forename: Jerry P
authors.initials: JP
authors.lastname: Palmer
mesh_terms: D000328:Adult; D002096:C-Peptide; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D003930:Diabetic Retinopathy / Q000378:metabolism; D005260:Female; D006442:Glycated Hemoglobin; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D013997:Time Factors; D055815:Young Adult
chemical_list: D002096:C-Peptide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin